Molecular mechanisms of testosterone action on the testis

Roberts, Kenneth P.; Chauvin, Theodore R.

doi:10.1016/j.coemr.2019.03.003

Cited by 8 publications

(3 citation statements)

References 39 publications

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“…We found that male Atp10A deficient mice have small testes ( Figures 2B,C ), oligozoospermia ( Figures 2D,F ) and spermatid degeneration ( Figure 3C ), a trend of decreased circulating levels of Inhibin B, a marker for spermatogenesis ( Anderson and Sharpe, 2000 ), and elevated circulating levels of testosterone ( Figure 4B ). The combination of small testes, oligozoospermia, and elevated testosterone levels appears paradoxical, as testosterone is a critical factor in facilitating testes growth and supporting spermatogenesis ( Kenneth et al, 2019 ). However, it is possible that the low sperm count could lead to a compensatory increase in testosterone production.…”

Section: Discussionmentioning

confidence: 99%

ATP10A deficiency results in male-specific infertility in mice

Norris,

Yazlovitskaya,

Yang

et al. 2024

Front. Cell Dev. Biol.

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Over 8% of couples worldwide are affected by infertility and nearly half of these cases are due to male-specific issues where the underlying cause is often unknown. Therefore, discovery of new genetic factors contributing to male-specific infertility in model organisms can enhance our understanding of the etiology of this disorder. Here we show that murine ATP10A, a phospholipid flippase, is highly expressed in male reproductive organs, specifically the testes and vas deferens. Therefore, we tested the influence of ATP10A on reproduction by examining fertility of Atp10A knockout mice. Our findings reveal that Atp10A deficiency leads to male-specific infertility, but does not perturb fertility in the females. The Atp10A deficient male mice exhibit smaller testes, reduced sperm count (oligozoospermia) and lower sperm motility (asthenozoospermia). Additionally, Atp10A deficient mice display testes and vas deferens histopathological abnormalities, as well as altered total and relative amounts of hormones associated with the hypothalamic-pituitary-gonadal axis. Surprisingly, circulating testosterone is elevated 2-fold in the Atp10A knockout mice while luteinizing hormone, follicle stimulating hormone, and inhibin B levels were not significantly different from WT littermates. The knockout mice also exhibit elevated levels of gonadotropin receptors and alterations to ERK, p38 MAPK, Akt, and cPLA2-dependent signaling in the testes. Atp10A was knocked out in the C57BL/6J background, which also carries an inactivating nonsense mutation in the closely related lipid flippase, Atp10D. We have corrected the Atp10D nonsense mutation using CRISPR/Cas9 and determined that loss of Atp10A alone is sufficient to cause infertility in male mice. Collectively, these findings highlight the critical role of ATP10A in male fertility in mice and provide valuable insights into the underlying molecular mechanisms.

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Section: Discussionmentioning

confidence: 99%

ATP10A deficiency results in male-specific infertility in mice

Norris,

Yazlovitskaya,

Yang

et al. 2024

Front. Cell Dev. Biol.

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“…Testosterone hormone is one of the essential reproductive hormones to regulate the spermatogenesis process. (42) Thus, this study has measured the level of testosterone hormone in the serum sample of the rats. The result showed that CCG treatments were significantly improved the level of testosterone if compared to the control group.…”

Section: Discussionmentioning

confidence: 99%

Effect of Croton caudatus Geiseler Aqueous Root Extract on Reproductive and Biochemical Parameters in Male Wistar Rats

et al. 2020

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BACKGROUND: Croton caudatus Geiseler (CCG), a local herb that empirically has been used as traditional medicine for malaria, fever, convulsions, and rheumatic arthritis. This study aimed to investigate the effect of CCG on reproductive and biochemical parameters in male Wistar rats.METHODS: Twenty-four Wistar male rats were divided randomly into four groups, which were treated with CCG aqueous root extract at the concentration of 0-16 mg/kg, via oral gavage. After 21 days of treatment, blood, sperm, and testes were harvested for analyses. Sperm parameters were evaluated using computer-assisted sperm analyser (Hamilton Thorne Sperm Analyzer), and morphometric analyses of histological changes were performed.RESULTS: CCG extract at 8 and 16 mg/kg significantly (p<0.05) increased the total sperm count, concentration, and motility; whereby, only 16 mg/kg significantly decreased the percentage of abnormal sperm morphology. Testosterone hormones levels were the highest in 4 mg/kg CCG but were slightly decreased in 8 and 16 mg/kg CCG. The histological results showed a significant increase in the germinal epithelial height, decrease of lumen size at 16 mg/kg of CCG extract. No significant changes of alanine aminotransferase (ALT) and creatinine levels in serum from all CCG extract groups. However, the aspartate aminotransferase (AST) level in 8 mg/kg CCG was elevated, and the blood urea nitrogen (BUN) level was decreased in all CCG extract groups.CONCLUSION: In conclusion, the CCG extract at 4 mg/kg has the potential to enhance spermatogenesis activity within the seminiferous tubules in rats without any hepatotoxicity and nephrotoxicity effect on the liver and kidney.KEYWORDS: Croton caudatus Geiseler, rats, spermatogenesis, seminiferous tubules, testis, testosterone

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“…It has been demonstrated that NR4A2 can recruit and activate transcription of the genes Steroidogenic Acute Regulatory protein (StAR) or 3β-hydroxysteroid dehydrogenase (3β-HSD) in Leydig cells [ 15 ]. Leydig cells produce some sex hormones, including testosterone and dihydrotestosterone, which are crucial for the male fetus, sexual behavior, sex accessory gland development and function, and initiation and maintenance of spermatogenesis [ 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

The Distribution, Expression Patterns and Functional Analysis of NR1D1 and NR4A2 in the Reproductive Axis Tissues of the Male Tianzhu White Yak

Dai

Zhang

Shi

et al. 2021

Animals

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Nuclear hormone receptors NR1D1 and NR4A2 play important roles in the synthesis and metabolism of hormones that are thought to be strictly regulated by the hypothalamus-pituitary-gonad axis (HPG) tissues via gene expression. However, in the yak, the function and regulatory mechanisms of NR1D1 and NR4A2 are not clearly understood. The current study is aimed to investigate the expression patterns, distribution and functions of these two receptors in HPG tissues in male Tianzhu white yaks. Immunohistochemical staining showed NR1D1 and NR4A2 proteins were present in all yak HPG tissues with differential expression patterns and degrees of staining, particularly in Leydig cells that were strongly positive in accordance with the immunofluorescence results. qRT-PCR and Western blot results suggested that the highest expression levels of NR1D1 and NR4A2 mRNA were present in the hypothalamus, while the expression levels of NR1D1 and NR4A2 proteins were higher in the testis and epididymis than in the hypothalamus or pituitary gland. In addition, expression levels of NR1D1 and NR4A2 mRNA and protein in testicular tissues differed by age. Expression levels were significantly higher at 6 years of age. Gene ontology (GO) and pathway analysis enrichment revealed that NR1D1 may directly regulate the synthesis and metabolism of steroid hormones via interaction with different targets, while NR4A2 may indirectly regulate the synthesis and metabolism of steroid hormones. These results showed that NR1D1 and NR4A2, as important mediators, are involved in the regulation of male yak reproduction, and especially of steroid hormones and androgen metabolism. These results will be helpful for the further understanding of the regulatory mechanisms of NR1D1 and NR4A2 in yak reproduction.

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Molecular mechanisms of testosterone action on the testis

Cited by 8 publications

References 39 publications

ATP10A deficiency results in male-specific infertility in mice

ATP10A deficiency results in male-specific infertility in mice

Effect of Croton caudatus Geiseler Aqueous Root Extract on Reproductive and Biochemical Parameters in Male Wistar Rats

The Distribution, Expression Patterns and Functional Analysis of NR1D1 and NR4A2 in the Reproductive Axis Tissues of the Male Tianzhu White Yak

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